Regulation of matrix metalloproteinases and their inhibitors by interferon-beta: a longitudinal study in multiple sclerosis patients

Mult Scler. 2009 Jun;15(6):721-7. doi: 10.1177/1352458509102920. Epub 2009 Apr 21.

Abstract

Background: Matrix metalloproteinases (MMPs) represent a large family of proteolytic enzymes, with some members being implicated in the immunopathogenesis of multiple sclerosis (MS). Interferon (IFN)-beta is one of the current mainstays in MS therapy and known to downregulate the expression of MMP-9. However, only sparse information is available on the effects of IFN-beta on the other 20 members of the MMP family.

Methods: This is a longitudinal analysis on the RNA expression pattern of all known MMPs and their endogenous inhibitors before and after 1 and 6 months of IFN-beta therapy. RNA expression levels were assessed in peripheral venous blood cells from 14 MS patients and 8 matched controls by real time-PCR.

Results: RNA expression levels before treatment differed in part in MS patients compared to healthy controls (MMP-9, MMP-14, MMP-19, TIMP-1, TIMP-2). Some of the MMPs responded to therapy specifically (MMP-8, MMP-9, MMP-19), whereas others remained unchanged over time.

Conclusions: These data suggest that MMPs may differ in their expression levels in MS patients and that this group of enzymes is differentially regulated during the treatment with IFN-beta in MS for at least 6 months.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Immunologic Factors / therapeutic use
  • In Vitro Techniques
  • Interferon-beta / therapeutic use*
  • Leukocytes / drug effects
  • Leukocytes / physiology
  • Longitudinal Studies
  • Male
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 8 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinases / genetics*
  • Matrix Metalloproteinases, Secreted / genetics
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*
  • Tissue Inhibitor of Metalloproteinase-2 / genetics*

Substances

  • Immunologic Factors
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Interferon-beta
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Secreted
  • matrix metalloproteinase 19
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 14